Damage to a peripheral nerve makes acts of daily life very inconvenient, if not impossible. For example, injury to the cavernosal nerve results in impotency.
A challenge in nerve repair is to restore continuity between the proximal and distal nerve stumps. When there is a nerve gap distance that must be bridged, it may be impossible to bring the cut nerve stumps into proximity close enough to achieve a direct suture repair. In this case, a certain type of intervening material must be used. The most commonly used material is an autograft of a peripheral nerve harvested from the patient, e.g., a sural nerve autograft. The surgical repair procedure is tedious and time-consuming. However, there is no alternative to the autograft at this time.
Therefore, it would be desirable to have an alternative nerve graft material that not only fulfills the requirements, but also overcomes many of the shortcomings, of a nerve autograft. Indeed, many types of biomaterials, natural or synthetic, have been used to make tubes or conduits for guiding peripheral nerve regeneration. Although this technology, which is commonly called xe2x80x9centubulation repair,xe2x80x9d has several theoretical advantages over nerve autografting, the results still are not satisfactory for repairing long nerve defects.
The tubes or conduits for guiding peripheral nerve regeneration are commonly made of materials such as polylactide, polylactide/polyglycolide copolymers, acrylic copolymers, polyvinylidene fluoride, polyglactin mesh, Millipore filter material, silicone, GORE-TEX(copyright) (expanded polytetrafluoroethylene), arterial cuffs, preformed mesothelial tubes or various other synthetic polyesters. The shortcomings of using a tube or conduit made of these materials include immune responses, induction of scar tissue, difficulty in application, and development of local elevated concentrations of compounds released after the degradation of a degradable material used in the device. For a tube or conduit made of non-degradable materials, e.g., polyvinylidene fluoride, a second surgery is often necessary for removal of the tube or conduit.
Further, although these devices are tubular, they do not all provide kink resistance. Kink resistance (i.e., resistance to forming a crease or a sharp bending of the wall) is particularly important in cases which require bending of the device for proper connections, such as nerve repairs in wrists and hands. Kinking of a nerve-guiding tube causes nerve compression and potential axonal disruption and neuroma formation.
In addition, certain devices are not effective to bridge a long gap distance, e.g. 2 cm or longer. Typically, their use results in a regenerated nerve cable that is thinner than desirable.
Further, the in vivo stability of certain implant devices for nerve repair is not clear. Thus, the utility of such implant devices is questionable in that they may prematurely fail and thus be unsuitable for methods involving longer gap nerve regeneration (e.g. longer than 2 cm).
Therefore, there is a need for a biocompatible, resorbable, semipermeable, and kink resistant tubular implant for nerve repair.
The present invention pertains to an implant device made of a biocompatible, bioresorbable, and biopolymeric material.
More specifically, the present invention relates to an implant device including a tubular matrix. The tubular matrix has a first end and a second end, a wall of a uniform thickness and disposed such that it forms ridges, and a channel which is defined by the wall of the matrix and extends from the first end to the second end of the matrix. The implant device can be utilized for tissue repair, including nerve repair, vascular repair, urological tissue repair, esophageal repair, and intestinal tissue repair.
One subset of the implant devices of this invention further include a plurality of cylindrical matrices made of a biocompatible and bioresorbable biopolymeric material. The cylindrical matrices are disposed inside the channel and parallel to the longitudinal axis of the tubular matrix. Each cylindrical matrix has two ends, a wall of a uniform thickness and disposed such that it forms a plurality of ridges, and a passage which is defined by its wall and extends from one end to the other end of the cylindrical matrix. One passage, or alternatively a plurality of passages, of a cylindrical matrix is of suitable dimension for receiving the nerve to be repaired. For example, the longitudinal passage dimension can be about 40-99% (e.g., about 40-95%, about 80-95%, about 60-95%, about 70-90%, about 50-90%, about 85-99%) of the dimension of the tubular matrix. The passage can alternatively be between about 0.01 mm and 1.0 mm in width. In one embodiment, the tubular matrix has an internal diameter of about 0.1 mm to 10 mm, a length of about 0.3 cm to 15 cm, and a thickness of about 0.02 mm to 1 mm; and each cylindrical matrix has an internal diameter of about 0.1 mm to 2 mm, a length of about 0.3 cm to 15 cm, and a thickness of about 0.02 mm to 1.0 mm; or alternatively an internal diameter of about 0.1 mm to 2 mm, a length of about 0.3 cm to 15 cm, and a thickness of about 0.02 mm to 0.5 mm.
Another subset of the implant devices of this invention further include a plurality of filaments made of a biocompatible and bioresorbable biopolymeric material, wherein the filaments are disposed inside the channel and parallel to the longitudinal axis of the tubular matrix, thereby forming inter-filamental spaces which extend along the tubular matrix; and at least one inter-filamental space is dimensioned for receiving the nerve to be repaired. For example, the filament length can be about 40-95% of the length of the tubular matrix. The inter-filamental space can alternatively be between about 0.01 mm and 1.0 mm in width. In one embodiment, the tubular matrix has an internal diameter of about 0.1 mm to 10 mm, a length of about 0.3 cm to 15 cm, and a thickness of about 0.02 mm to 1 mm; and each filament has a diameter of about 0.03 mm to 0.5 mm and a length of about 0.3 cm to 15 cm.
Still another subset of the implant devices of this invention further include one or more porous cylindrical matrices made of a biocompatible and bioresorbable biopolymeric material. A porous matrix refers to a solid material that contains pores. The pore size for the porous matrix can be from about 10 xcexcm to about 800 xcexcm, alternatively it can be from about 10 xcexcm to about 500 xcexcm, alternatively from about 20 xcexcm to about 300 xcexcm. The porous cylindrical matrices are disposed inside the channel of the tubular matrix and parallel to the tubular matrix. Each porous cylindrical matrix has two ends and at least one passage which is parallel to its longitudinal axis and extending from one end to the other end of the porous cylindrical matrix. One passage of a porous cylindrical matrix is of suitable dimension for receiving the nerve to be repaired. For example, the porous cylindrical matrix length can be about 40-95% of the length of the tubular matrix. The passage can alternatively be between about 0.01 mm and 1.0 mm in width. In one embodiment, the tubular matrix has an internal diameter of about 0.1 mm to 10 mm, a length of about 0.3 cm to 15 cm, and a thickness of about 0.02 mm to 1 mm; each porous cylindrical matrix has a diameter of about 0.1 mm to 10 mm and a length of about 0.3 cm to 15 cm; and each passage of each porous cylindrical matrix has a diameter of about 0.1 mm to 2 mm and a length of about 0.3 cm to 15 cm; alternatively each porous cylindrical matrix has a diameter of about 1 mm to 5 mm.
The invention also relates to a method of preparing a ridged tubular matrix. The method includes the following steps: fabricating a tubular matrix comprising biopolymeric fibers; drying the tubular matrix; humidifying the tubular matrix; pressing the tubular matrix along its longitudinal axis to cause formation of ridges on the wall thereof; and crosslinking the biopolymeric fibers to obtain a ridged tubular matrix. In an alternate aspect, the method may comprise a ridge formation step including fabricating the fibers using a ridged mandrel, in place of the pressing of the tubular matrix step to cause ridge formation. The term xe2x80x9cfabricatingxe2x80x9d refers to any method of manufacturing the matrix with or without the aid of an instrument.
In another embodiment, the implant device (e.g., tubular matrix) has an internal diameter of about 1 mm to 5 mm, alternatively about 1 mm to 4.5 mm, alternatively about 1 mm to 4 mm, alternatively about 1 mm to 3 mm, in combination with any of the length and thickness dimensions delineated herein.
In another embodiment, the implant device (e.g., tubular matrix) has a length of about 0.3 cm to 15 cm, alternatively about 0.3 cm to 10 cm, alternatively about 0.3 cm to 5 cm in combination with any of the diameter and thickness dimensions delineated herein.
In one embodiment, the implant device of the invention has a length from about 1 cm to 15 cm, internal diameter from about 1 mm to 10 mm and thickness from about 0.2 mm to 1 mm, alternatively it has an internal diameter of about 0.1 mm to 10 mm, a length of about 0.3 cm to 15 cm, and a thickness of about 0.02 mm to 1 mm.
The details of several embodiments of the invention are set forth in the accompanying drawings and the description below. Other features, objects, and advantages of the invention will be apparent from the description and drawings, and from the claims.